AB0093 COMPLEMENT IN THE DIAGNOSIS OF AXIAL SPONDYLOARTHRITIS (AXSPA). INVESTIGATIONS IN A CROSS-SECTIONAL COHORT (OPTIREF) OF PATIENTS SUSPECTED OF AXIAL SPONDYLOARTHRITIS
Authors: C. E. Mistegaard, A. Troldborg, A. G. Loft, S. Thiel, L. Spiller, V. Rios Rodriguez, B. Muche, J. Rademacher, A. K. Weber, S. Lueders, J. Sieper, D. Poddubnyy, F. Proft
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease without specific diagnostic biomarkers. However, recent evidence suggests an involvement of the innate immune system in the pathogenesis of axSpA [1]. The lectin pathway of complement activation serves essential functions in the innate immune system, regulates homeostasis and development. We have previously shown the lectin pathway proteins (LPPs) L-ficolin and M-ficolin to be elevated in axSpA-patients compared with clinically relevant controls with unspecific low back pain (uLBP). <h3>Objectives</h3> To investigate the diagnostic potential of LPP levels in patients recruited from a well-defined cross-sectional prospective cohort (OptiRef), including newly diagnosed axSpA-patients and uLBP-patients. <h3>Methods</h3> Serum samples were obtained from 515 individuals from the OptiRef cohort; 151 newly diagnosed axSpA-patients and 364 uLBP-patients [2]. All patients were assessed according to a standardized protocol, incl. clinical information as demographics, SpA features, symptom duration, and disease activity. Routine lab tests (HLA-B27 and CRP) were performed. Imaging (x-ray and MRI) was performed if deemed clinically relevant. Serum levels of all 10 LPPs (MBL, CL-L1, M-ficolin, H-ficolin, L-ficolin, MASP-1, MASP-2, MASP-3, MAp19, and MAp44) and the complement activation product C3dg were measured by immunoassays. <h3>Results</h3> Patient characteristics are shown in Table 1. L-ficolin, MASP-2, and C3dg serum levels were increased in axSpA-patients compared with uLBP-patients, whereas CL-L1 and MASP-3 serum levels were decreased (Figure 1). After adjustments for CRP, C3dg serum levels remained significantly increased in axSpA-patients, whereas M-ficolin and MASP-3 serum levels were decreased in axSpA-patients. The diagnostic potential of combining either L-ficolin, MASP-3, and C3dg with HLA-B27 increased specificity to 93-95% compared with HLA-B27 alone (77%) but decreased sensitivity to 29-33% compared with HLA-B27 alone (83%). In a univariate logistic regression analysis, CL-L1, MASP-2, MASP-3, and C3dg were associated with an axSpA-diagnosis, and C3dg and MASP-3 remained significant in a multivariate logistic regression analysis. <h3>Conclusion</h3> In this study, serum levels of C3dg, MASP-3, and CL-L1 differed significantly between axSpA-patients and uLBP-patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3, and C3dg increased diagnostic specificity for axSpA, it seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with the axSpA-diagnosis in multivariate logistic regression, indicating the complement system's involvement in axSpA-pathogenesis. This should be further investigated. <h3>References</h3> [1]Ambarus, C., et al. Curr Opin Rheumatol. 2012 [2]Poddubnyy, D., et al. Rheumatology (Oxford). 2021 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Clara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft: None declared, Steffen Thiel: None declared, Laura Spiller: None declared, Valeria Rios Rodriguez: None declared, Burkhard Muche: None declared, Judith Rademacher: None declared, Anne-Katrin Weber: None declared, Susanne Lueders: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB.